Lineage Tracing Reveals a Subset of Reserve Muscle Stem Cells Capable of Clonal Expansion under Stress
Open accessAbstract
Stem cell heterogeneity is recognized as functionally relevant for tissue homeostasis and repair. The identity, context dependence, and regulation of skeletal muscle satellite cell (SC) subsets remains poorly understood. We identify a minor subset of Pax7+ SCs that is indelibly marked by an inducible Mx1-Cre transgene in vivo, is enriched for Pax3 expression, and has reduced ROS (reactive oxygen species) levels. Mx1+ SCs possess potent stem cell activity upon transplantation but minimally contribute to endogenous muscle repair, due to their relative low abundance. In contrast, a dramatic clonal expansion of Mx1+ SCs allows extensive contribution to muscle repair and niche repopulation upon selective pressure of radiation stress, consistent with reserve stem cell (RSC) properties. Loss of Pax3 in RSCs increased ROS content and diminished survival and stress tolerance. These observations demonstrate that the Pax7+ SC pool contains a discrete population of radiotolerant RSCs that undergo clonal expansion under severe stress.
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A subset of MuSCs identified by inducible Mx1-Cre lineage tracing is particularly resistant to stress, perhaps representing a population protected from ageing.
“Another subset of MuSCs (identified by inducible Mx1–Cre lineage tracing) is particularly resistant to stress36, perhaps also representing a population that is protected from ageing37.”
From Ageing and rejuvenation of tissue stem cells and their niches (2023) · cites this paper as [36]
A population of stress-resistant, highly regenerative Pax3+ MuSCs overlaps with LRCs.
“We recently identified a population of stress-resistant, highly regenerative Pax3+ MuSCs that overlap with LRCs (Scaramozza et al., 2019).”
From Aging induces aberrant state transition kinetics in murine muscle stem cells (2020) · cites this paper as Scaramozza et al., 2019
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References 61 · Cited by 93
- Authors
- Scaramozza, A., Park, D., Kollu, S., Beerman, I., Sun, X., Rossi, D. J., Lin, C. P., Scadden, D. T., Crist, C., & Brack, A. S.
- Affiliations
- University of California, San Francisco (US)
- Baylor College of Medicine (US)
- Massachusetts General Hospital (US)
- Harvard University (US)
- Jewish General Hospital (CA)
- Corresponding author
- Brack, Andrew S.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 24
- Issue
- 6
- Pages
- 944-957.e5
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC6597014
- OpenAlex
- W2936875025
- Cited by
- 93
- References
- 61
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 16 · 2022: 15 · 2021: 20 · 2020: 12 · 2019: 7
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Foundation for the National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- skeletal muscle stem cells, clonal expansion, Pax7, Pax3, reactive oxygen species, radiation stress, muscle repair, stem cell heterogeneity, stem cell transplantation
- MeSH terms
- PAX3 Transcription Factor, Animals, Cell Differentiation, Cell Survival, Clone Cells, DNA Damage, Humans, Mice, Inbred C57BL, Radiation, Ionizing, Regeneration, Up-Regulation, Reactive Oxygen Species, Cell Lineage, Satellite Cells, Skeletal Muscle, Mice, PAX7 Transcription Factor, Adult Stem Cells, Myxovirus Resistance Proteins
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